Bridging critical nerve defects through an acellular homograft seeded with autologous Schwann cells obtained from a regeneration neuroma of the proximal stump
Bridging critical nerve defects through an acellular homograft seeded with autologous Schwann cells obtained from a regeneration neuroma of the proximal stump
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DOI：
10.1055/s-2008-1076091
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发表时间：
2008-04-01
影响因子：
2.1
通讯作者：
Frey, Manfred
中科院分区：
文献类型：
--
作者：
Aszmann, Oskar C.;Korak, Klaus J.;Frey, Manfred
在过去的十年中，一些模型已经研究了不同生物和/或合成基质作为传统神经移植物替代品的有效性。尽管如此，轴突再生在较长的距离上（大约3厘米）没有发生。一个问题可能是，促进生长的环境不仅包括物理线索，还包括仅由反应性雪旺细胞提供的丰富的不同生长因子谱。在目前的研究中，我们研究了在大鼠模型中，由第一代自体雪旺细胞组成的杂交移植物是否可以帮助严重神经缺损的再生。在这种情况下，雪旺细胞不是在体外扩增的，而是在重建时从近端残端神经瘤中提取，然后植入无细胞的自体或自体移植物中。重建12周后，通过功能肌肉测试、常规组织学、组织形态计量学和逆行示踪技术对再生进行量化。结果表明，无论雪旺细胞是移植到自体基质上还是移植到同源脱细胞基质上，都能在整个距离内成功再生。两个移植物中都有雪旺细胞；然而，只有感觉轴突持续了整个距离。功能结果很差，没有运动和感觉恢复。同种基质对照组C不含雪旺细胞，无定向轴突再生迹象。对照组D采用自体逆行移植物，如预期的那样恢复良好。本实验试图创建一种杂交移植物，其中近端残端神经瘤用作自体雪旺细胞的生物资源，将其植入非细胞基质中，从而为再生轴突提供物理和化学支持。结果令人鼓舞，在整个距离内都观察到成功的再生；然而，只有感觉轴突具有足够的再生潜能，才能与末端器官进行接触。对于运动轴突，还需要进一步改进导管的制备。
Over the last decade, several models have investigated the usefulness of different biologic and/or synthetic matrices as alternatives to conventional nerve grafts. Still, axonal regeneration did not occur over longer (> 3 cm) distances. One problem may be that a growth-promoting environment not only includes physical cues but also a rich spectrum of different growth factors only provided by reactive Schwann cells. In the current study, we investigated whether a hybrid graft consisting of first-generation autologous Schwann cells seeded onto an acellular auto- or homograft can aid regeneration across a critical nerve defect in a rat model. In this paradigm, Schwann cells were not expanded in vitro but harvested from the proximal stump neuroma at the time of reconstruction and seeded into either an acellular home- or autograft. Regeneration was then quantitated with functional muscle testing, regular histology, histomorphometry, and retrograde tracing techniques 12 weeks after reconstruction. Results showed successful regeneration over the entire distance regardless of whether Schwann cells were transplanted onto auto- or homologous acellular matrix. Schwann cells did populate both grafts; however, only sensory axons persisted through the entire distance. The functional outcome was dismal with no motor and poor sensory recovery. Control group C with homologous matrix only without Schwann cells showed no signs of directed axonal regeneration. Control group D with autologous reverse graft showed excellent recovery, as was expected. The present experiment sought to create a hybrid graft where the proximal stump neuroma is used as a biological resource for autologous Schwann cells that are seeded unto an acellular matrix, thus providing both physical and chemical support to regenerating axons. The results are encouraging in that successful regeneration was observed over the entire distance; however, only sensory axons had enough regenerative potential to also make end-organ contact. For motor axons, further refinements in conduit preparation have to be done.